A Comprehensive Protocol for Microbead-Induced Ocular Hypertension in Mice.

Glaucoma is a common optic neuropathy characterized by degeneration of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP), that is, ocular hypertension, is the primary modifiable risk factor for glaucoma and the primary characteristic of most preclinical glaucoma models. Extensive genotype and phenotype diversity at relatively low cost and high accessibility makes laboratory mice an excellent preclinical model for glaucoma.

Early inner plexiform layer thinning and retinal nerve fiber layer thickening in excitotoxic retinal injury using deep learning-assisted optical coherence tomography.

Excitotoxicity from the impairment of glutamate uptake constitutes an important mechanism in neurodegenerative diseases such as Alzheimer's, multiple sclerosis, and Parkinson's disease. Within the eye, excitotoxicity is thought to play a critical role in retinal ganglion cell death in glaucoma, diabetic retinopathy, retinal ischemia, and optic nerve injury, yet how excitotoxic injury impacts different retinal layers is not well understood. Here, we investigated the longitudinal effects of N-methyl-D-aspartate (NMDA)-induced excitotoxic retinal injury in a rat model using deep learning-assisted retinal layer thickness estimation.

Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi-Ethnic Study of Atherosclerosis (MESA).

Introduction: Retinal vascular network changes may reflect the integrity of the cerebral microcirculation, and may be associated with cognitive impairment.

Methods: Associations of retinal vascular measures with cognitive function and MRI biomarkers were examined amongst Multi-Ethnic Study of Atherosclerosis (MESA) participants in North Carolina who had gradable retinal photographs at Exams 2 (2002 to 2004, n = 313) and 5 (2010 to 2012, n = 306), and detailed cognitive testing and MRI at Exam 6 (2016 to 2018).

Results: After adjustment for covariates and multiple comparisons, greater arteriolar fractal dimension (FD) at Exam 2 was associated with less isotropic free water of gray matter regions (β = -0.

Retinoprotective compounds, current efficacy, and future prospective.

Retinal dysfunction is the most common cause of vision loss in several retinal disorders. It has been estimated a great increase in these pathologies that are becoming more globally widespread and numerous over time, also supported by the life expectancy increment. Among different types of retinopathies, we can account some that share causes, symptoms, and treatment including diabetic retinopathy, age-related macular degeneration, glaucoma, and retinitis pigmentosa.

Internalization of Angiotensin-(1-12) in Adult Retinal Pigment Epithelial-19 Cells.

Angiotensin-(1-12) [Ang-(1-12)] serves as a primary substrate to generate angiotensin II (Ang II) by angiotensin-converting enzyme and/or chymase suggests it may be an unrecognized source of Ang II-mediated microvascular complication in hypertension-mediated retinopathy. We investigated Ang-(1-12) expression and internalization in adult retinal pigment epithelial-19 (ARPE-19) cultured cells. We performed the internalization of Ang-(1-12) in ARPE-19 cells in the presence of a highly specific monoclonal antibody (mAb) developed against the C-terminal end of the Ang-(1-12) sequence.

Reverse translation of artificial intelligence in glaucoma: Connecting basic science with clinical applications.

Artificial intelligence (AI) has been approved for biomedical research in diverse areas from bedside clinical studies to benchtop basic scientific research. For ophthalmic research, in particular glaucoma, AI applications are rapidly growing for potential clinical translation given the vast data available and the introduction of federated learning. Conversely, AI for basic science remains limited despite its useful power in providing mechanistic insight.

Deep learning and optical coherence tomography in glaucoma: Bridging the diagnostic gap on structural imaging.

Glaucoma is a leading cause of progressive blindness and visual impairment worldwide. Microstructural evidence of glaucomatous damage to the optic nerve head and associated tissues can be visualized using optical coherence tomography (OCT). In recent years, development of novel deep learning (DL) algorithms has led to innovative advances and improvements in automated detection of glaucomatous damage and progression on OCT imaging.

A novel approach to sclerotomy closure in pars plana vitrectomy: a pilot study.

Background: Methods of sclerotomy closure following a vitrectomy, including the use of sutures, have been associated with complications such as inflammation, foreign body sensation, and infection. Here, we test an innovative approach to scleral wound closure following pars plana vitrectomy that involves plugging the wound. We investigated several materials with the intent of using products that were either already approved by the FDA for other types of procedures or were biocompatible patient-derived materials.

Interleukin-6 promotes microtubule stability in axons via Stat3 protein-protein interactions.

The interleukin-6 (IL-6) family of cytokines and its downstream effector, STAT3, are important mediators of neuronal health, repair, and disease throughout the CNS, including the visual system. Here, we elucidate a transcription-independent mechanism for the neuropoietic activities of IL-6 related to axon development, regeneration, and repair. We examined the outcome of IL-6 deficiency on structure and function of retinal ganglion cell (RGC) axons, which form the optic projection.

Impairment of Membrane Repolarization Accompanies Axon Transport Deficits in Glaucoma.

Glaucoma is a leading cause of blindness worldwide, resulting from degeneration of retinal ganglion cells (RGCs), which form the optic nerve. In glaucoma, axon transport deficits appear to precede structural degeneration of RGC axons. The period of time between the onset of axon transport deficits and the structural degeneration of RGC axons may represent a therapeutic window for the prevention of irreversible vision loss.

Pressure-dependent modulation of inward-rectifying K channels: implications for cation homeostasis and K dynamics in glaucoma.

Glaucoma is the leading cause of blindness worldwide, resulting from degeneration of retinal ganglion cells (RGCs), which form the optic nerve. Prior to structural degeneration, RGCs exhibit physiological deficits. Müller glia provide homeostatic regulation of ions that supports RGC physiology through a process called K siphoning.

Phenotypes of primary retinal macroglia: Implications for purification and culture conditions.

Many neurodegenerations, including those of the visual system, have complex etiologies that include roles for both neurons and glia. In the retina there is evidence that retinal astrocytes play an important role in neurodegeneration. There are several approaches for isolating and growing primary retinal astrocytes, however, they often lead to different results.

The relationship between the Young's modulus and dry etching rate of polydimethylsiloxane (PDMS).

Polydimethylsiloxane (PDMS) has been the pivotal materials for microfluidic technologies with tremendous amount of lab-on-a-chip devices made of PDMS microchannels. While molding-based soft-lithography approach has been extremely successful in preparing various PDMS constructs, some complex features have to been achieved through more complicated microfabrication techniques that involve dry etching of PDMS. Several recipes have been reported for reactive ion etching (RIE) of PDMS; however, the etch rates present large variations, even for the same etching recipe, which poses challenges in adopting this process for device fabrication.

Ccl5 Mediates Proper Wiring of Feedforward and Lateral Inhibition Pathways in the Inner Retina.

The β-chemokine Ccl5 and its receptors are constitutively expressed in neurons of the murine inner retina. Here, we examined the functional and structural significance of this constitutive Ccl5 signaling on retinal development. We compared outcomes of electrophysiology, ocular imaging and retinal morphology in wild-type mice (WT) and mice with Ccl5 deficiency ( ).

Increased bioavailability of cyclic guanylate monophosphate prevents retinal ganglion cell degeneration.

The nitric oxide - guanylyl cyclase-1 - cyclic guanylate monophosphate (NO-GC-1-cGMP) pathway has emerged as a potential pathogenic mechanism for glaucoma, a common intraocular pressure (IOP)-related optic neuropathy characterized by the degeneration of retinal ganglion cells (RGCs) and their axons in the optic nerve. NO activates GC-1 to increase cGMP levels, which are lowered by cGMP-specific phosphodiesterase (PDE) activity. This pathway appears to play a role in both the regulation of IOP, where reduced cGMP levels in mice leads to elevated IOP and subsequent RGC degeneration.

Impact of Graphene on the Efficacy of Neuron Culture Substrates.

How graphene influences the behavior of living cells or tissues remains a critical issue for its application in biomedical studies, despite the general acceptance that graphene is biocompatible. While direct contact between cells and graphene is not a requirement for all biomedical applications, it is often mandatory for biosensing. Therefore, it is important to clarify whether graphene impedes the ability of cells to interact with biological elements in their environment.

The nitric oxide-guanylate cyclase pathway and glaucoma.

Glaucoma is a prevalent optic neuropathy characterized by the progressive dysfunction and loss of retinal ganglion cells (RGCs) and their optic nerve axons, which leads to irreversible visual field loss. Multiple risk factors for the disease have been identified, but elevated intraocular pressure (IOP) remains the primary risk factor amenable to treatment. Reducing IOP however does not always prevent glaucomatous neurodegeneration, and many patients progress with the disease despite having IOP in the normal range.

The Microbead Occlusion Model of Ocular Hypertension in Mice.

Glaucoma is a common optic neuropathy that leads to vision loss through the degeneration of retinal ganglion cells (RGCs) and their axons. RGC degeneration in glaucoma is associated with sensitivity to intraocular pressure (IOP) and elevated IOP (also known as ocular hypertension) is the primary modifiable risk factor. Ocular hypertension is the primary characteristic of rodent models for glaucoma research.

Constitutive and Stress-induced Expression of CCL5 Machinery in Rodent Retina.

Signaling by inflammatory cytokines and chemokines is associated with neurodegeneration in disease and injury. Here we examined expression of the β-chemokine CCL5 and its receptors in the mouse retina and evaluated its relevance in glaucoma, a common optic neuropathy associated with sensitivity to intraocular pressure (IOP). Using quantitative PCR, fluorescent hybridization, immunohistochemistry and quantitative image analysis, we found CCL5 mRNA and protein was constitutively expressed in the inner retina and synaptic layers.

Interleukin-6 Deficiency Attenuates Retinal Ganglion Cell Axonopathy and Glaucoma-Related Vision Loss.

The pleotropic cytokine interleukin-6 (IL-6) is implicated in retinal ganglion cell (RGC) survival and degeneration, including that associated with glaucoma. IL-6 protects RGCs from pressure-induced apoptosis . However, it is unknown how IL-6 impacts glaucomatous degeneration .

Oral Delivery of a Synthetic Sterol Reduces Axonopathy and Inflammation in a Rodent Model of Glaucoma.

Glaucoma is a group of optic neuropathies associated with aging and sensitivity to intraocular pressure (IOP). The disease is the leading cause of irreversible blindness worldwide. Early progression in glaucoma involves dysfunction of retinal ganglion cell (RGC) axons, which comprise the optic nerve.

Probing electrical signals in the retina via graphene-integrated microfluidic platforms.

Graphene has attracted extensive attention in biological and biomedical fields due to its unique physical properties and excellent biocompatibility. We combine graphene field-effect transistors and scanning photocurrent microscopy with microfluidic platforms to investigate electrical signals in mouse retina. Remarkable photocurrent signals were detected from the graphene underneath the optic nerve head (ONH) of the retina, where the electrical activity from this region can modulate the carrier concentration of the graphene and induce local potential gradients.